title: Human snRNA genes use polyadenylation factors to promote efficient transcription termination.
abstract: RNA polymerase II transcribes both protein coding and non-coding RNA genes and, in yeast, different mechanisms terminate transcription of the two gene types. Transcription termination of mRNA genes is intricately coupled to cleavage and polyadenylation, whereas transcription of small nucleolar (sno)/small nuclear (sn)RNA genes is terminated by the RNA-binding proteins Nrd1, Nab3 and Sen1. The existence of an Nrd1-like pathway in humans has not yet been demonstrated. Using the U1 and U2 genes as models, we show that human snRNA genes are more similar to mRNA genes than yeast snRNA genes with respect to termination. The Integrator complex substitutes for the mRNA cleavage and polyadenylation specificity factor complex to promote cleavage and couple snRNA 3'-end processing with termination. Moreover, members of the associated with Pta1 (APT) and cleavage factor I/II complexes function as transcription terminators for human snRNA genes with little, if any, role in snRNA 3'-end processing. The gene-specific factor, proximal sequence element-binding transcription factor (PTF), helps clear the U1 and U2 genes of nucleosomes, which provides an easy passage for pol II, and the negative elongation factor facilitates termination at the end of the genes where nucleosome levels increase. Thus, human snRNA genes may use chromatin structure as an additional mechanism to promote efficient transcription termination in vivo.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK and CGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3PT, UK.
authors.forename: Dawn
authors.initials: D
authors.lastname: O'Reilly
authors.forename: Olga V
authors.initials: OV
authors.lastname: Kuznetsova
authors.forename: Clelia
authors.initials: C
authors.lastname: Laitem
authors.forename: Justyna
authors.initials: J
authors.lastname: Zaborowska
authors.forename: Martin
authors.initials: M
authors.lastname: Dienstbier
authors.forename: Shona
authors.initials: S
authors.lastname: Murphy
mesh_terms: D002843:Chromatin / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D026721:RNA 3' End Processing; D012342:RNA, Small Nuclear / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology; D061806:Transcription Termination, Genetic; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism*
chemical_list: D002843:Chromatin; D012342:RNA, Small Nuclear; C106703:SNAPC protein complex, human; D014157:Transcription Factors; C405483:U1 small nuclear RNA; D039221:mRNA Cleavage and Polyadenylation Factors